• Mitsuaki Nishikimi, Atsushi Numaguchi, Kunihiko Takahashi, Yasuhiro Miyagawa, Kota Matsui, Michiko Higashi, Go Makishi, Shigeyuki Matsui, and Naoyuki Matsuda.
• Department of Emergency and Critical Care, Nagoya University Graduate School of Medicine, Nagoya, Japan.
• Crit. Care Med. 2018 Jul 1; 46 (7): 1099-1105.

ObjectivesOccurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients.DesignA single-center, triple-blinded, randomized placebo-controlled trial.SettingICU of an academic hospital.PatientsEligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission.InterventionsThe intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU.Measurements And Main ResultsA total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings.ConclusionsRamelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly.

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